@article{915db1d75b8c44129ea2feebe44cca12,
title = "Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial",
abstract = "Background & Aims Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Methods Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Results Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P <.0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Conclusions Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035.",
keywords = "DAA, EPO, Erythropoiesis, Side Effect",
author = "Fred Poordad and Eric Lawitz and Reddy, {K. Rajender} and Afdhal, {Nezam H.} and Christophe H{\'e}zode and Stefan Zeuzem and Lee, {Samuel S.} and Calleja, {Jose Luis} and Brown, {Robert S.} and Antonio Craxi and Heiner Wedemeyer and Lisa Nyberg and Nelson, {David R.} and Lorenzo Rossaro and Luis Balart and Morgan, {Timothy R.} and Bacon, {Bruce R.} and Flamm, {Steven L.} and Kowdley, {Kris V.} and Weiping Deng and Koury, {Kenneth J.} and Pedicone, {Lisa D.} and Dutko, {Frank J.} and Burroughs, {Margaret H.} and Katia Alves and Janice Wahl and Brass, {Clifford A.} and Albrecht, {Janice K.} and Sulkowski, {Mark S.}",
note = "Funding Information: Conflicts of interest The authors disclose the following: F. Poordad has received consultancy fees from Merck, Vertex, Abbott, Gilead, Achillion, Bristol Myers Squibb, Boehringer Ingelheim, Genentech, Novartis, and Janssen/Tibotec; has grants/grants pending from Abbott Laboratories, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, Sanofi-Aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics; and has received payment for development of educational presentations and speaker fees from Merck, Abbott, Achillion, Genentech, Vertex, Salix. and Gilead. E. Lawitz has received clinical research grants from Abbott Laboratories , Achillion Pharmaceuticals , Anadys Pharmaceuticals , Biolex Therapeutics , Boehringer Ingelheim , Bristol Myers Squibb , Gilead Sciences , GlaxoSmithKline , GlobeImmune, Idenix Pharmaceuticals , Idera Pharmaceuticals , Inhibitex Pharmaceuticals , Medarex , Medtronic , Merck , Novartis, Pharmasset , Roche , Sanofi-Aventis , Schering-Plough , Santaris Pharmaceuticals , Scynexis Pharmaceuticals , Tibotec , Vertex Pharmaceuticals , ViroChem Pharma , ZymoGenetics ; and payment for lectures, including service on speakers bureaus for Merck. K. R. Reddy has received consultancy fees from Roche, Merck, Vertex, Janssen, Gilead, Abbvie, Idenix, and Bristol Myers Squibb; has grants/grants pending from Merck, Roche, Vertex, Janssen, Gilead, Abbvie, Bristol Myers Squibb; and payment for development of educational presentations from ViralEd. N. H. Afdhal has received grant support from Merck, Gilead, Vertex, GSK, Abbott, BMS, and Pharmasett . He has been a scientific advisor or consultant for Gilead, Vertex, Merck, Novartis, Tibotec, Johnson and Johnson, Medgenics, and Springbank; has stock/stock options in Springbank and Medgenics; and is Editor of the Journal of Viral Hepatitis. C. H{\'e}zode reports membership of the French National Board and payment for lectures including service on speaker's bureaus for French National Meetings. S. Zeuzem has received consultancy fees from Abbott, Anadys, Bristol-Myers Squibb, Gilead, HGS, Merck, Novartis, Pharmasset, Pfizer, Roche, Tibotec, and Vertex; and lecture honoraria/member of speaker's bureau for Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche. S. S. Lee declares consulting for Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Janssen, Merck, Novartis, Roche, Vertex; research support from Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Merck, Roche, Novartis, Roche, Vertex ; and has been a speaker for Bristol Myers Squibb, Gilead, Merck and Roche. J. L. Calleja has received consultancy fees from Gilead, Janssen, Merck, Novartis, Roche, Bristol Myers Squibb; and has received speaker fees from Gilead, Merck, and Roche. R. S. Brown has received grant/research support from Gilead, Janssen, Novartis, Salix, Schering/Merck, and Vertex ; and has done speaking and teaching for Salix Pharmaceuticals, Roche/Genentech, Gilead, and Schering/Merck. A. Craxi has received financial support from Merck to conduct the clinical trial. H. Wedemeyer has received clinical research grants from Abbott , Bristol Myers Squibb , Gilead , Merck , Novartis, Roche , Roche Diagnostics , Siemens ; has received consultancy fees from Abbott, Abvie, Biolex, Bristol Myers Squibb, Boehringer Ingelheim, Gilead, ITS, JJ/Janssen-Cilag, Medgenics, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, ViiV; has been a scientific advisor or consultant for Abbott, Abvie, Biolex, Bristol Myers Squibb, Boehringer Ingelheim, Gilead, ITS, JJ/Janssen-Cilag, Medgenics, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene; has received payment for development of educational presentations and speaker fees from Abbott, Bristol Myers Squibb, Gilead, ITS, JJ/Janssen-Cilag, Merck/Schering-Plough, Novartis, Roche; and has received payment for lectures including service on speakers bureaus for Abbott, Bristol Myers Squibb, Gilead, ITS, JJ/Janssen-Cilag, Merck/Schering-Plough, Novartis and Roche. L. Nyberg has received research grants from Merck , Gilead , Abbott , Pharmasset , Roche/Genentech/Anadys , Vertex , Bristol-Myers-Squibb , Human Genome Sciences , and Idenix/Novartis ; Speakers Bureau for Merck. D. Nelson has received clinical research grants from Merck and has grants/grants pending from Abbott, Bayer, Boehringer Ingelheim, Gilead, Janssen and Vertex. L. Rossaro has grants/grants pending from Roche, Genentech, Vertex, Merck, Novartis, Gilead, Pharmasset, and Bristol Myers Squibb; payment for lectures including service on speakers bureaus for Onyx, Salix, Vertex, Merck, Roche, and Genentech. L. Balart reports having received grant support and support for travel to meetings for the study or other purposes from Merck; and payment for lecture fees including service on speaker's bureaus from Merck, Genentech, and Bristol Myers Squibb. T. Morgan has grant/grants pending from Bristol Myers Squibb, Merck, Roche/Genentech, Pharmasset, Gilead, and Vertex. B. R. Bacon has received consultancy fees from Gilead, Kadmon Pharmaceuticals, Valeant, Vertex, and Human Genome Sciences; has grants and grants pending from Roche, Gilead, Bristol Myers Squibb, Kadmon Pharmaceuticals, Valeant, Vertex, Human Genome Sciences, Wyeth, and Romark Laboratories; payment for lectures including service on speakers bureaus for Kadmon Pharmaceuticals, Gilead, and Merck; and served on Data and Safety Monitoring Boards for Novartis, ISIS, Vertex, and Gilead. S. L. Flamm has received grants from Merck , Vertex , Gilead , Novartis , Anadys , Achillion , Tibotec , Bristol Myers Squibb, and AbbVie ; consultancy fees from Vertex, Gilead, Novartis, Bristol Myers Squibb, and AbbVie; and payment for lectures including service on speakers bureaus from Merck and Vertex. K. V. Kowdley has received a grant from Merck ; has grants/grants pending from Bristol Myers Squibb, Intercept, Abbott, Gilead, Merck, Mochida, Conatus, Boehringer Ingelheim, Ikaria, Vertex, Janssen, and Beckman; has received royalties from Up-to-Date; has received payment for development of educational presentations from CME Outfitters and ViralEd, and for serving on advisory boards for Gilead, Abbott, Vertex, and Merck; and has received consultancy fees from Novartis, which were paid to his institution. W. Deng, K. J. Koury, F. J. Dutko, M. H. Burroughs, K. Alves, and J. Wahl are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc, Whitehouse Station, NJ and hold stock and/or stock options. L. D. Pedicone is a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc, Whitehouse Station, NJ and holds stock and/or stock options and is now at Focus Medical Communications. C. A. Brass is a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc Whitehouse Station, NJ and holds stock and/or stock options. Now at Novartis. J. K. Albrecht is a former employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Whitehouse Station, NJ and holds stock and/or stock options. M. S. Sulkowski has received consultancy fees and has grants/grants pending from Abbott, Bristol Myers Squibb, Boehringer-Ingelheim, Gilead, Janssen, Merck, Novartis, Pfizer, and Vertex. ",
year = "2013",
month = nov,
doi = "10.1053/j.gastro.2013.07.051",
language = "English (US)",
volume = "145",
pages = "1035--1044.e5",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",
}
